molecules Review Genus Periploca (Apocynaceae): A Review of Its Classification, Phytochemistry, Biological Activities and Toxicology 1,2, , 3, 1,2 4 Mingjin Huang y *, Shoumao Shen y, Chunli Luo and Yan Ren 1 College of Agriculture, Guizhou University, Guiyang 550025, Guizhou, China 2 State Key Laboratory of Propagation and Cultivation on Medicinal Plants of Guizhou Province, Guiyang 550025, Guizhou, China 3 School of Pharmacy, Yancheng Teachers’ University, Yancheng 224002, Jiangsu, China 4 College of Pharmacy, Guizhou University, Guiyang 550025, Guizhou, China * Correspondence: [email protected]; Tel.: +86-851-8385-4014 These authors contributed equally to this work. y Received: 25 June 2019; Accepted: 23 July 2019; Published: 29 July 2019 Abstract: The genus Periploca belongs to the family Apocynaceae, which is composed of approximately ten species of plants according to incomplete statistics. Most of these plants serve as folk medicines with a long history, especially Periploca sepium and Periploca forrestii. The botanical classifications, chemical constituents, biological activities and toxicities of the genus Periploca were summarized in the literature from 1897 to early 2019. Though the botanical classification of this genus is controversial, these species are well-known to be rich sources of diverse and complex natural products—above all, cardiac steroids and C21 pregnane steroids with special structures and obvious pharmacological activities. The various crude extracts and 314 isolated metabolites from this genus have attracted much attention in intensive biological studies, indicating that they are equipped with cardiotonic, anti-inflammatory, immunosuppressive, antitumor, antimicrobial, antioxidant, insecticidal and other properties. It is noteworthy that some cardiac glycosides showed hepatotoxicity and cardiotoxicity at certain doses. Therefore, in view of the medical and agricultural value of the genus Periploca, in-depth investigations of the pharmacology in vivo, the mechanisms of biological actions, and the pharmacokinetics of the active ingredients should be carried out in the future. Moreover, in order to ensure the safety of clinical medication, the potential toxicities of cardiac glycosides or other compounds should also be paid attention. This systematic review provides an important reference base for applied research on pharmaceuticals and pesticides from this genus. Keywords: genus Periploca; phytochemistry; biological activities; classification; toxicology; review 1. Introduction The genus Periploca belongs to the family Apocynaceae [1] and involves approximately ten species which are diffusely distributed in temperate Asia, southern Europe and tropical Africa [2]. Many species of this genus have been historically used as folk medicines in China, especially Periploca sepium and Periploca forrestii. The root bark of P. sepium, known as “Xiangjiapi” or “Bei-wujiapi,” is utilized as a traditional Chines medicine (TCM) for the treatment of rheumatoid arthritis and bone and muscle pain, which is recorded in the Chinese Pharmacopoeia (2015 version). The processing of Cortex Periplocae requires removing impurities, cleaning, slicing, and drying. The dried Cortex Periplocae (3~6 g) and other medicinal materials are decocted in water and taken for internal use [3]. The stems or the whole plant of P. forrestii, which is a well-known herb known as “Heiguteng,” are widely used by the Miao nationality in China to treat many diseases, including rheumatic arthritis, traumatic injury, Molecules 2019, 24, 2749; doi:10.3390/molecules24152749 www.mdpi.com/journal/molecules Molecules 2019, 24, 2749 2 of 50 Molecules 2019, 24, x FOR PEER REVIEW 2 of 47 stomachache,decocted in dyspepsia, water or soaked and amenorrhea. in wine for Theinternal usage use, of P.forrestii or it is smashedis usually for decocted external in application water or soaked [4]. The in winetitle genus for internal is abundant use, or itwith is smashed an array for of externalattractive application metabolites, [4]. such The title as steroids, genus is abundantoligosaccharides, with anterpenoids, array of attractive phenylpropanoids, metabolites, suchand flavonoids. as steroids, These oligosaccharides, novel and complex terpenoids, metabolites phenylpropanoids, and various andcrude flavonoids. extracts Thesefrom the novel genus and Periploca complex have metabolites attracted and increasing various crudeattention extracts to intensive from the biological genus Periplocastudies,have indicating attracted that increasing they possess attention significan to intensivet cardiotonic, biological anti-inflammatory, studies, indicating immunosuppressive, that they possess significantantitumor, cardiotonic, antimicrobial, anti-inflammatory, antioxidant, immunosuppressive,insecticidal and other antitumor, properties. antimicrobial, Some cardenolide-type antioxidant, insecticidalsteroids exhibit and other obvious properties. cardiotonic Some cardenolide-type and antitumor steroidseffects exhibitat a certain obvious dose. cardiotonic Their andstrong antitumorimmunosuppression effects at a certain anddose. insecticidal Their strong potentials immunosuppression provide new development and insecticidal prospects potentials for providepregnane newglycosides. development In addition, prospects cardiac for pregnane steroids glycosides. were also fo Inund addition, to have cardiac latent steroidstoxicity. were In the also 2000s, found several to haveresearchers latent toxicity. provided In the reviews 2000s, severalof the chemical researchers cons providedtituents reviewsand biological of the chemical activities constituents of the genus andPeriploca biological [5,6]. activities However, of the these genus concisePeriploca reviews[5,6]. were However, expressed these concisein Chinese. reviews Additionally, were expressed a large in Chinese.amount of Additionally, scientific research a large results amount on ofthis scientific genus has research emerged results in recent on this years. genus To hasmake emerged researchers in recentknow years. elaborate To make information researchers on know the chemical elaborate and information biological on activities the chemical of the and genus biological Periploca activities and to ofmake the genus a modestPeriploca contributionand to make to the a rational modest applicatio contributionn of tothis the genus, rational a systematic application review of this of the genus, genus a systematicPeriploca is review imperative. of the genusWe coveredPeriploca topicsis imperative. including Wethe coveredbotanical topics classification, including phytochemistry, the botanical classification,biological activities phytochemistry, and toxicology biological of the activities genus andPeriploca toxicology through of thea literature genus Periploca survey fromthrough 1897 a to literatureearly 2019. survey The from outline 1897 of tothis early paper 2019. and The some outline representative of this paper plants and of some the representativegenus Periploca plants are shown of thein genus FigurePeriploca 1. are shown in Figure1. FigureFigure 1. 1.The The outline outline and and some some representative representative plants plants of of the the genus genusPeriploca Periploca.. (Left:(Left: TheThe fruitsfruits ofof P. P. forrestiiforrestii;; Centre: Centre: The The flowers flowers of ofP. P. sepium sepium; Right:; Right: The The stems stems of ofP. P. forrestii forrestii. The. The center center and and right right pictures pictures werewere downloaded downloaded from from Plant Plant Photo Photo Bank Bank of China,of China, PPBC.). PPBC.). 2. Botanical Classification of the Genus Periploca 2. Botanical Classification of the Genus Periploca In 1895, Schumann was the first to classify the P. species. Browicz defined the genus Periploca and In 1895, Schumann was the first to classify the P. species. Browicz defined the genus Periploca recognized eleven species in 1966. According to Flora of China (1995) [2], the genus Periploca comprises and recognized eleven species in 1966. According to Flora of China (1995) [2], the genus Periploca about ten species, and five species are distributed in China. Additionally, in 1997, Venter [7] suggested comprises about ten species, and five species are distributed in China. Additionally, in 1997, Venter correcting the nomenclature of Periploca to provide diagnostic characteristics for the genus and to [7] suggested correcting the nomenclature of Periploca to provide diagnostic characteristics for the improve classification. However, fourteen species belonging to genus Periploca were recorded by Venter, genus and to improve classification. However, fourteen species belonging to genus Periploca were not including P. forrestii, which largely grows in southern China. Moreover, several Chinese scholars recorded by Venter, not including P. forrestii, which largely grows in southern China. Moreover, are interested in the taxonomy of this genus. Periploca omeiensis Z. Y. Zhu, which is merely distributed several Chinese scholars are interested in the taxonomy of this genus. Periploca omeiensis Z. Y. Zhu, in Emei Mountain, China, was identified as a new species by Zhu in 1991 [8]. Furthermore, another which is merely distributed in Emei Mountain, China, was identified as a new species by Zhu in 1991 [8]. Furthermore, another new species, named Periploca chrysantha D. S. Yao, X. C. Chen et J. W. Ren, Molecules 2019, 24, 2749 3 of 50 new species, named Periploca chrysantha D. S. Yao, X. C. Chen et J. W. Ren, was found in Gansu, China in 2002